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Antimicrob Agents Chemother. 2011 Jul;55(7):3498-504. doi: 10.1128/AAC.01622-10. Epub 2011 May 16.

Developmental pharmacokinetics of lamivudine in 580 pediatric patients ranging from neonates to adolescents.

Author information

  • 1EA 3620, Université Paris Descartes, Paris, France. naim.bouazza@cch.aphp.fr

Abstract

Lamivudine concentration-time courses were described for a very large range of ages to study the effects of body weight and maturation on lamivudine pharmacokinetics and to check the consistency of dosing recommendations. Lamivudine concentrations were monitored on a routine basis to produce concentrations similar to the known values in adults. Concentrations were measured in 580 children from 2 days to 18 years old. A total of 2,106 plasma lamivudine concentrations were measured, and a population pharmacokinetic analysis was performed using the stochastic approximation expectation maximization algorithm implemented in MONOLIX 3.1 software. A two-compartment model adequately described the data. After standardization for a mean standard body weight by using an allometric model, age also had a significant effect on clearance maturation. Typical population estimates (percent interindividual variability) standardized for 70 kg of the apparent clearance, including central and peripheral volumes of distribution, intercompartmental clearance, and absorption rate constant, were 31 liters · h(-1) (32%), 76.4 liters (77%), 129 liters, 5.83 liters · h(-1), and 0.432 h(-1), respectively. According to the model, elimination clearance (liters/h/70 kg) increases gradually during the first years of life. Theoretical doses needed to reach the range of 24 h of exposure observed in adults were calculated: to be closer to adult exposure, children should receive 4 mg/kg/day from birth to 8 weeks of age, 5 mg/kg/day from 8 to 16 weeks of age, 6 mg/kg from 16 to 25 weeks of age, 8 mg/kg/day from 25 weeks of age to 14 kg of body weight, 150 mg/day from 14 to 25 kg of body weight, 225 mg/day from 25 to 35 kg of body weight, and 300 mg/day thereafter.

PMID:
21576443
[PubMed - indexed for MEDLINE]
PMCID:
PMC3122471
Free PMC Article

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